Test plates having one or more individual wells or reaction chambers are common laboratory tools. Such devices are employed for a wide variety of purposes and assays, see U.S. Pat. No. 4,902,481. Single welled devices are also well known, see U.S. Pat. Nos. 3,483,768, 4,632,761 and 4,722,792.
The plate filtration devices include two plates, the upper plate, commonly referred to as the well plate and a lower plate, commonly referred to as the underdrain. The well plate contains one or more individual wells that are open at one end and have a filtration membrane sealed across the opposite end. The underdrain is provided with a second set of individual well(s), which register with the wells of the well plate. Each of the wells in the underdrain have an open end and a second end which contains a small opening having a spout which opening and spout are designed to receive liquid which passes through the filtration membrane of the upper plate. The size of the opening and the spout are controlled so that liquid is retained in the well plate above the membrane under normal atmospheric conditions due to surface tension forces but passes through the membrane and the opening and spout when a pressure differential is applied across the membrane.
The filtration media has been secured to the lower portion of the well plate in several ways. In one method, a sheet of filtration membrane is stretch across the bottom of the well plate and adhered to each of the individual well or wells. In a second method, individual membrane pieces are cut and placed within the interior of the well where either friction or an undercut is used to maintain the position of the membrane in the well. In a third common method, the individual pieces are adhered to the bottom portion of the individual wells of the well plate.
The first method has problems in that liquid that passes through the membrane can travel laterally between wells and contaminate adjacent wells. The second method relies upon proper placement and maintenance of that placement in the well over time. Vibration, rough handling and other factors can displace the membrane causing loss of the sample or at least a portion of the sample or liquid within the sample. Additonally, it fails to form an integral seal such that liquid may bypass the filter altogether resulting in loss of product and contamination of the filtrate. The third method has been the preferred and most commonly used method as it ensures that there is no cross talk or contamination between the wells and there is a true seal of the membrane to the well plate so as to prevent leakage.
In these devices, the membrane has been limited to microporous membrane or a glass fiber depth filter or other coarse filtration media. This is due to the nature of the membrane and its ability to be sealed to the bottom of the well in the well plate. Other membranes, in particular ultrafiltration (UF) membranes are mentioned as being of possible use, however they have not been successfully sealed within the well plate. This is due to the structure and composition of the UF membranes. These membranes are relatively thin and fragile. Therefore these membranes are typically cast upon a support structure such as a non-woven porous sheet or a microporous membrane. The UF membrane itself is a relatively thin, dense material which is extremely sensitive to any type of mechanical or chemical bonding method.
What is desired is a plate system which allows for the use of membranes other than microporous membranes and which contains all of the advantages of the prior plates, namely avoiding lateral flow and contamination between the wells and the use of multiple wells in the same device. The present invention provides such a device.